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Phylogenetic measures of indel rate variation among the HIV-1 group M subtypes.

ABSTRACT: The transmission fitness and pathogenesis of HIV-1 is disproportionately influenced by evolution in the five variable regions (V1-V5) of the surface envelope glycoprotein (gp120). Insertions and deletions (indels) are a significant source of evolutionary change in these regions. However, the rate and composition of indels has not yet been quantified through a large-scale comparative analysis of HIV-1 sequences. Here, we develop and report results from a phylogenetic method to estimate indel rates for the gp120 variable regions across five major subtypes and two circulating recombinant forms (CRFs) of HIV-1 group M. We processed over 26,000 published HIV-1 gp120 sequences, from which we extracted 6,605 sequences for phylogenetic analysis. We reconstructed time-scaled phylogenies by maximum likelihood and fit a binomial-Poisson model to the observed distribution of indels between closely related pairs of sequences in each tree (cherries). By focusing on cherries in each tree, we obtained phylogenetically independent indel reconstructions, and the shorter time scales in cherries reduced the bias due to purifying selection. Rate estimates ranged from 3.0×10-5 to 1.5×10-3 indels/nt/year and varied significantly among variable regions and subtypes. Indel rates were significantly lower in V3 relative to V1, and were also lower in HIV-1 subtype B relative to the 01_AE reference. We also found that V1, V2, and V4 tended to accumulate significantly longer indels. Furthermore, we observed that the nucleotide composition of indels was distinct from the flanking sequence, with higher frequencies of G and lower frequencies of T. Indels affected N-linked glycosylation sites more often in V1 and V2 than expected by chance, consistent with positive selection on glycosylation patterns within these regions. These results represent the first comprehensive measures of indel rates in HIV-1 gp120 across multiple subtypes and CRFs, and identifies novel and unexpected patterns for further research in the molecular evolution of HIV-1.

SUBMITTER: Palmer J

PROVIDER: S-EPMC6642732 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Phylogenetic measures of indel rate variation among the HIV-1 group M subtypes.

Palmer John J Poon Art F Y AFY

Virus evolution 20190721 2

The transmission fitness and pathogenesis of HIV-1 is disproportionately influenced by evolution in the five variable regions (V1-V5) of the surface envelope glycoprotein (gp120). Insertions and deletions (indels) are a significant source of evolutionary change in these regions. However, the rate and composition of indels has not yet been quantified through a large-scale comparative analysis of HIV-1 sequences. Here, we develop and report results from a phylogenetic method to estimate indel rate ...[more]

PMID: 31341641

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Project description:BACKGROUND: Recent phylogenetic studies have revealed that the mitochondrial genome of the angiosperm Silene noctiflora (Caryophyllaceae) has experienced a massive mutation-driven acceleration in substitution rate, placing it among the fastest evolving eukaryotic genomes ever identified. To date, it appears that other species within Silene have maintained more typical substitution rates, suggesting that the acceleration in S. noctiflora is a recent and isolated evolutionary event. This assessment, however, is based on a very limited sampling of taxa within this diverse genus. RESULTS: We analyzed the substitution rates in 4 mitochondrial genes (atp1, atp9, cox3 and nad9) across a broad sample of 74 species within Silene and related genera in the tribe Sileneae. We found that S. noctiflora shares its history of elevated mitochondrial substitution rate with the closely related species S. turkestanica. Another section of the genus (Conoimorpha) has experienced an acceleration of comparable magnitude. The phylogenetic data remain ambiguous as to whether the accelerations in these two clades represent independent evolutionary events or a single ancestral change. Rate variation among genes was equally dramatic. Most of the genus exhibited elevated rates for atp9 such that the average tree-wide substitution rate for this gene approached the values for the fastest evolving branches in the other three genes. In addition, some species exhibited major accelerations in atp1 and/or cox3 with no correlated change in other genes. Rates of non-synonymous substitution did not increase proportionally with synonymous rates but instead remained low and relatively invariant. CONCLUSION: The patterns of phylogenetic divergence within Sileneae suggest enormous variability in plant mitochondrial mutation rates and reveal a complex interaction of gene and species effects. The variation in rates across genomic and phylogenetic scales raises questions about the mechanisms responsible for the evolution of mutation rates in plant mitochondrial genomes.

Project description:BackgroundThe effect of alignment gaps on phylogenetic accuracy has been the subject of numerous studies. In this study, we investigated the relationship between the total number of gapped sites and phylogenetic accuracy, when the gaps were introduced (by means of computer simulation) to reflect indel (insertion/deletion) events during the evolution of DNA sequences. The resulting (true) alignments were subjected to commonly used gap treatment and phylogenetic inference methods.Results(1) In general, there was a strong--almost deterministic--relationship between the amount of gap in the data and the level of phylogenetic accuracy when the alignments were very "gappy", (2) gaps resulting from deletions (as opposed to insertions) contributed more to the inaccuracy of phylogenetic inference, (3) the probabilistic methods (Bayesian, PhyML & "MLepsilon, " a method implemented in DNAML in PHYLIP) performed better at most levels of gap percentage when compared to parsimony (MP) and distance (NJ) methods, with Bayesian analysis being clearly the best, (4) methods that treat gapped sites as missing data yielded less accurate trees when compared to those that attribute phylogenetic signal to the gapped sites (by coding them as binary character data--presence/absence, or as in the MLepsilon method), and (5) in general, the accuracy of phylogenetic inference depended upon the amount of available data when the gaps resulted from mainly deletion events, and the amount of missing data when insertion events were equally likely to have caused the alignment gaps.ConclusionWhen gaps in an alignment are a consequence of indel events in the evolution of the sequences, the accuracy of phylogenetic analysis is likely to improve if: (1) alignment gaps are categorized as arising from insertion events or deletion events and then treated separately in the analysis, (2) the evolutionary signal provided by indels is harnessed in the phylogenetic analysis, and (3) methods that utilize the phylogenetic signal in indels are developed for distance methods too. When the true homology is known and the amount of gaps is 20 percent of the alignment length or less, the methods used in this study are likely to yield trees with 90-100 percent accuracy.

Project description:Background and objectivesAlthough HIV sequence clustering is routinely used to identify subpopulations experiencing elevated transmission, it over-simplifies transmission dynamics and is sensitive to methodology. Complementarily, viral diversification rates can be used to approximate historical transmission rates. Here, we investigated the concordance and sensitivity of HIV transmission risk factors identified by phylogenetic clustering, viral diversification rate, changes in viral diversification rate and a combined approach.MethodologyViral sequences from 9848 people living with HIV in British Columbia, Canada, sampled between 1996 and February 2019, were used to infer phylogenetic trees, from which clusters were identified and viral diversification rates of each tip were calculated. Factors associated with heightened transmission risk were compared across models of cluster membership, viral diversification rate, changes in diversification rate, and viral diversification rate among clusters.ResultsViruses within larger clusters had higher diversification rates and lower changes in diversification rate than those within smaller clusters; however, rates within individual clusters, independent of size, varied widely. Risk factors for both cluster membership and elevated viral diversification rate included being male, young, a resident of health authority E, previous injection drug use, previous hepatitis C virus infection or a high recent viral load. In a sensitivity analysis, models based on cluster membership had wider confidence intervals and lower concordance of significant effects than viral diversification rate for lower sampling rates.Conclusions and implicationsViral diversification rate complements phylogenetic clustering, offering a means of evaluating transmission dynamics to guide provision of treatment and prevention services.Lay summaryUnderstanding HIV transmission dynamics within clusters can help prioritize public health resource allocation. We compared socio-demographic and clinical risk factors associated with phylogenetic cluster membership and viral diversification rate, a historical branching rate, in order to assess their relative concordance and sampling sensitivity.

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Phylogenetic measures of indel rate variation among the HIV-1 group M subtypes.

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Phylogenetic measures of indel rate variation among the HIV-1 group M subtypes.

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